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Elevated cytokine and chemokine levels in the placenta are associated with in-utero HIV-1 mother-to-child transmission

Kumar, Surender B.a; Rice, Cara E.b; Milner, Danny A. Jrc; Ramirez, Nilsa C.d; Ackerman, William E. IVe; Mwapasa, Victorf; Turner, Abigail Norrisa,g; Kwiek, Jesse J.a,g,h

doi: 10.1097/QAD.0b013e3283519b00
Basic Science

Objective: To determine whether there is an association between cytokine and chemokine levels in plasma isolated from the placenta and HIV-1 mother-to-child transmission (MTCT).

Design: We designed a case–control study of HIV-infected, pregnant women enrolled in the Malaria and HIV in Pregnancy cohort. Participants were recruited in Blantyre, Malawi, from 2000 to 2004. Patients were women whose children were HIV-1 DNA-positive at birth (in-utero MTCT) or HIV-1 DNA-negative at birth and HIV-1 DNA-positive at 6 weeks postpartum (intrapartum MTCT); controls were women whose children were HIV-1 DNA-negative both at birth and 6 weeks postpartum.

Methods: After delivery, blood was isolated from an incision on the basal plate of the placenta. We used a Bio-Plex human cytokine assay (Bio-Rad, Hercules, California USA) to simultaneously quantify 27 cytokines, chemokines and growth factors in placental plasma. HIV-1 RNA copies were quantified with the Roche Amplicor kit.

Results: Levels of interleukin (IL) 4, IL-5, IL-6, IL-7, IL-9, eotaxin, IL-1Ra and interferon gamma-induced protein 10 (IP-10) were significantly elevated in placental plasma isolated from cases of in-utero HIV-1 MTCT. In contrast, only granulocyte colony-stimulating factor was elevated in placental plasma isolated from cases of intrapartum MTCT. After adjusting for maternal age, gestational age and peripheral CD4+ T-cell count, every log10 increase in placental IP-10 was associated with a three-fold increase in the prevalence of in-utero HIV-1 MTCT.

Conclusion: Elevated cytokine and chemokine levels in placental plasma were associated with in-utero and not intrapartum MTCT. IP-10, which is both a T-cell chemokine and potentiator of HIV-replication, was robustly and independently associated with prevalent, in-utero MTCT.

aThe Center for Microbial Interface Biology, The Center for Retrovirus Research

bDivision of Epidemiology, College of Public Health, The Ohio State University, Columbus, Ohio

cDepartment of Pathology, Brigham & Women's Hospital, Boston, Massachusetts

dDepartment of Pathology and Laboratory Medicine and the Biopathology Center, The Research Institute at Nationwide Children's Hospital, Columbus

eDepartment of Obstetrics and Gynecology, College of Medicine, The Ohio State University, Columbus, Ohio, USA

fDepartment of Community Health, Malawi College of Medicine, Blantyre, Malawi

gDivision of Infectious Diseases, Department of Medicine

hDepartment of Microbial Infection and Immunity and the Department of Microbiology, The Ohio State University, Columbus, Ohio, USA.

Correspondence to Jesse J. Kwiek, 1008 Biomedical Research Tower, 460 West 12th Avenue, Columbus, OH 43210, USA. Tel: +1 614 292 3256; fax: +1 614 292 9616; e-mail:

Received 7 September, 2011

Revised 28 December, 2011

Accepted 19 January, 2012

This research was presented in part at the 17th Conference on Retroviruses and Opportunistic Infections, San Francisco, California, USA (abstract 903).

© 2012 Lippincott Williams & Wilkins, Inc.